Outcomes for adults with KMT2A-r acute myeloid leukemia treated with venetoclax plus azacitidine (Ven/Aza) or intensive chemotherapy (IC): A single-center retrospective study.

e18537 Background: KMT2A-rearranged acute myeloid leukemia (KMT2A-r AML) is known for adverse outcomes due to aggressive disease presentation and high relapse rates. Oral menin inhibitors are being studied in combination with frontline chemotherapy regimens. However, baseline data regarding outcomes for KMT2A-r AML treated with Ven/Aza is limited. Here, we conducted a study to assess outcomes in newly diagnosed KMT2A-r AML treated with Ven/Aza or IC. Methods: We retrospectively analyzed outcomes for adults with KMT2A-r AML who received Ven/Aza or IC as their first therapy. Phenotype was assessed by Hematopathology by morphologic review and flow cytometry. A monocytic phenotype was defined by >20% monocytic differentiation within the blast population on morphology and expression of at least 2 of the following: CD14, CD64, CD11b, and CD11c. Responses were recorded based on 2022 ELN criteria. Statistical analyses were performed on R v4.4.2. Results: This study included 34 pts with KMT2A-r AML, with 50% receiving Ven/Aza (n = 17) and 50% receiving IC (n = 17). The median age was 46 (19-78) years (y), with the IC cohort being relatively younger (41 vs 57y for Ven/Aza; p = 0.01). 76% of pts had de novo AML, while 24% had therapy-related AML (t-AML). Most pts (79%) had a monocytic phenotype. The composite complete remission (CRc) rate was 35% in pts who received Aza/Ven and 82% in pts who received IC (p=0.005). Among the entire cohort, the median overall survival (mOS) was 17 months (mo) (95% CI 8.4 mo, NR), and the median event-free survival (mEFS) was 5.2 mo (3.7 mo, NR). The mOS was 8.8 mo (3.5 mo, NR) in pts treated with Ven/Aza and 37 mo (9.3 mo, NR) in pts treated with IC (p=0.27). The mEFS was 3.8 mo (2.0 mo, NR) in pts treated with Ven/Aza and 37 mo (4.6 mo, NR) in pts treated with IC (p=0.072). In multivariate analyses, Allo-HSCT was associated with a reduced risk of relapse (HR 0.09 (95% CI 0.03–0.33, p < 0.001)) and decreased risk of death (HR 0.17 (95% CI 0.05–0.52, p < 0.001)). t-AML was associated with an increased risk of death with a HR of 3.03 (95% CI 1.16–7.95, p = 0.02). Conclusions: Our results demonstrate that KMT2A-r is associated with a monocytic phenotype and highlights poor outcomes in KMT2A-r AML when treated with Ven/Aza as frontline therapy. Allo-HSCT independently improves the likelihood for long term survival. Whether the addition of a menin inhibitor to frontline chemotherapy will improve outcomes is being assessed in multiple clinical trials. Characteristics and responses for KMT2A-r AML. Variables Ven/AzaN = 17 IC 1 N = 17 P-value Median age, yrs 57 41 0.01 t-AML, n (%) 6 (35) 2 (12) 0.2 Monocytic phenotype, n (%) 12 (71) 15 (88) 0.4 Response, n (%)- CR- CRi- No response- UnknownCRc (CR + CRi) 5 (33)1 (6.7)9 (60)26 (35) 13 (81)1 (6.3)2 (13)114 (82) 0.007 0.005 1 IC regimens included 7+3 (n=13), 7+3 with midostaurin (n=1), FLAG-Ida+Ven (n=3).